Pro-apoptotic cascade activates BID, which oligomerizes BAK or BAX into pores that result in the release of cytochrome c

Citation
Sj. Korsmeyer et al., Pro-apoptotic cascade activates BID, which oligomerizes BAK or BAX into pores that result in the release of cytochrome c, CELL DEAT D, 7(12), 2000, pp. 1166-1173
Citations number
56
Categorie Soggetti
Cell & Developmental Biology
Journal title
CELL DEATH AND DIFFERENTIATION
ISSN journal
13509047 → ACNP
Volume
7
Issue
12
Year of publication
2000
Pages
1166 - 1173
Database
ISI
SICI code
1350-9047(200012)7:12<1166:PCABWO>2.0.ZU;2-8
Abstract
We review data supporting a model in which activated tBID results in an all osteric activation of BAK, inducing its intramembranous oligomerization int o a proposed pore for cytochrome c efflux, The BH3 domain of tBID is not re quired for targeting but remains on the mitochondrial surface where it is r equired to trigger BAK to release cytochrome c. tBID functions not as a por e-forming protein but as a membrane targeted and concentrated death ligand, tBID induces oligomerization of BAK, and both Bid and Bak knockout mice in dicate the importance of this event in the release of cytochrome c. In para llel, the full pro-apoptotic member BAX, which is highly homologous to BAK, rapidly forms pores in liposomes that release intravesicular FITC-cytochro me c similar to 20 Angstrom. A definable pore progressed from similar to 11 Angstrom consisting of two BAX molecules to a similar to 22 Angstrom pore comprised of four BAX molecules, which transported cytochrome c. Thus, an a ctivation cascade of pro-apoptotic proteins from BID to BAK or BAX integrat es the pathway from surface death receptors to the irreversible efflux of c ytochrome c.